Horm Metab Res 2020; 52(09): 647-653
DOI: 10.1055/a-1207-1132
Endocrine Care

Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours

Delphine Van Laethem
1   Endocrinology, Universitair Ziekenhuis Brussel, Brussel, Belgium
,
Alex Michotte
2   Department of Pathology (Neuropathology), Universitair Ziekenhuis Brussel, Brussel, Belgium
,
Wilfried Cools
3   Statistics, Vrije Universiteit Brussel, Brussel, Belgium
,
Brigitte Velkeniers
1   Endocrinology, Universitair Ziekenhuis Brussel, Brussel, Belgium
,
David Unuane
1   Endocrinology, Universitair Ziekenhuis Brussel, Brussel, Belgium
,
C. E. Andreescu
1   Endocrinology, Universitair Ziekenhuis Brussel, Brussel, Belgium
,
Bert Bravenboer
1   Endocrinology, Universitair Ziekenhuis Brussel, Brussel, Belgium
› Author Affiliations

Abstract

The aim of this study is to assess differences in patient characteristics, tumour characteristics and hormone levels between acromegalic patients with and without hyperprolactinemia. 44 patients of the University Hospital of Brussels, Belgium with acromegaly who were diagnosed between January 2007 and July 2018 were included in this study. Nineteen patients were classified in the hyperprolactinemia group and 25 patients were classified in the normoprolactinemia group. No significant differences between acromegalic patients with and without hyperprolactinemia were found in age at diagnosis, gender, presence of hyperprolactinemia symptoms, insulin-like growth factor 1, growth hormone and testosterone levels, tumour volume, tumour invasiveness, immunohistochemistry of growth hormone and prolactin, Ki-67 index and mitotic index. However, for a cut-off of 10% of prolactin-positive cells, there was a trend towards a higher percentage of prolactin-positive tumours in hyperprolactinemia patients (p=0.054) and higher mean prolactin level in case of positive prolactin immunostaining (p=0.007)). In our study there were no differences in characteristics between acromegaly patients with hyper- and normoprolactinemia. An association between the serum prolactin level and the positivity of prolactin immunohistochemistry of the adenoma tissue was found. The absence of a difference in tumour volume between patients with hyper- and normoprolactinemia suggests that the hyperprolactinemia is likely to be caused by the co-secretion of growth hormone and prolactin by the tumour. Finally, for the first time, the cut-off of 10% of prolactin cells was validated for the diagnosis of somatolactotroph tumours in acromegaly.



Publication History

Received: 01 November 2019

Accepted: 17 June 2020

Article published online:
05 August 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary 1999; 2: 29-41
  • 2 Abreu A, Tovar AP, Castellanos R. et al. Challenges in the diagnosis and management of acromegaly: A focus on comorbidities. Pituitary 2016; 19: 448-457
  • 3 Colao A, Ferone D, Marzullo P. et al. Systemic complications of acromegaly: Epidemiology, pathogenesis, and management. Endocr Rev 2004; 25: 102-152
  • 4 Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest 2009; 119: 3189-3202
  • 5 Trepp R, Stettler C, Zwahlen M. et al. Treatment outcomes and mortality of 94 patients with acromegaly. Acta Neurochir (Wien) 2005; 147: 243-251
  • 6 Mortini P, Losa M, Barzaghi R. et al. Results of transsphenoidal surgery in a large series of patients with pituitary adenoma. Neurosurgery 2005; 56: 1222-1233
  • 7 Evran M, Sert M, Tetiker T. Clinical experiences and success rates of acromegaly treatment: the single center results of 62 patients. BMC Endocr Disord 2014; 14: 97
  • 8 Melmed S, Jameson JL. Anterior Pituitary Tumor Syndromes. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J, Ed Harrison’s Principles of Internal Medicine. New York: McGraw-Hill Education; 2015: 2261–2274
  • 9 Voit D, Saeger W, Ludecke DK. Pituitary adenomas in acromegaly: Comparison of different adenoma types with clinical data. Endocr Pathol 1999; 10: 123-135
  • 10 Andersen M, Hagen C, Frystyk J. et al. Development of acromegaly in patients with prolactinomas. Eur J Endocrinol 2003; 149: 17-22
  • 11 De Marinis L, Zuppi P, Valle D. et al. A retrospective hormonal and immunohistochemical evaluation of 47 acromegalic patients: Prognostic value of preoperative plasma prolactin. Horm Metab Res 2002; 34: 137-143
  • 12 Kreutzer J, Vance ML, Lopes MB. et al. Surgical management of GH-secreting pituitary adenomas: An outcome study using modern remission criteria. J Clin Endocrinol Metab 2001; 86: 4072-4077
  • 13 Nyquist P, Laws ER, Elliott E. Novel features of tumors that secrete both growth hormone and prolactin in acromegaly. Neurosurgery 1994; 35: 179-183. discussion 183–174
  • 14 Wang M, Mou C, Jiang M. et al. The characteristics of acromegalic patients with hyperprolactinemia and the differences in patients with merely GH-secreting adenomas: Clinical analysis of 279 cases. Eur J Endocrinol 2012; 166: 797-802
  • 15 Mete O, Lopes MB. Overview of the 2017 WHO Classification of Pituitary Tumors. Endocr Pathol 2017; 28: 228-243
  • 16 Katznelson L, Laws ER, Melmed S. et al. Acromegaly: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99: 3933-3951
  • 17 Arafat AM, Mohlig M, Weickert MO. et al. Growth hormone response during oral glucose tolerance test: The impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls, and the role of gender, age, and body mass index. J Clin Endocrinol Metab 2008; 93: 1254-1262
  • 18 Frystyk J, Freda P, Clemmons DR. The current status of IGF-I – a 2009 update. Growth Horm IGF Res 2010; 20: 8-18
  • 19 Chuang CC, Lin SY, Pai PC. et al. Different volumetric measurement methods for pituitary adenomas and their crucial clinical significance. Sci Rep 2017; 7: 40792
  • 20 Davies BM, Carr E, Soh C. et al. Assessing size of pituitary adenomas: A comparison of qualitative and quantitative methods on MR. Acta Neurochir (Wien) 2016; 158: 677-683
  • 21 Scheithauer BW, Kovacs KT, Laws ER. et al. Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 1986; 65: 733-744
  • 22 Villa C, Vasiljevic A, Jaffrain-Rea ML. et al. A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): A European Pituitary Pathology Group (EPPG) proposal. Virchows Archiv 2019; 475: 687-692
  • 23 Bex M, Abs R, T’Sjoen G. et al. AcroBel - The Belgian registry on acromegaly: A survey of the “real-life” outcome in 418 acromegalic subjects. Eur J Endocrinol 2007; 157: 399-409
  • 24 Trouillas J, Sassolas G, Guigard MP. et al. Relationships between pathological diagnosis and clinical parameters in acromegaly. Metabolism 1996; 45: 53-56
  • 25 Furuhata S, Kameya T, Otani M. et al. Prolactin presents in all pituitary tumors of acromegalic patients. Hum Pathol 1993; 24: 10-15
  • 26 Tuna MM, Karakiliç E, Basaran MB. et al. Immunostaining results of growth hormone secreting adenomas and their correlation with laboratory findings. Turkish Journal of Endocrinology and Metabolism 2016; 20: 69-71
  • 27 Kuhn E, Chanson P. Cabergoline in acromegaly. Pituitary 2017; 20: 121-128
  • 28 Trouillas J, Vasiljevic A, Lapoirie M. et al. Pathological markers of somatotroph pituitary neuroendocrine tumors predicting the response to medical treatment. Minerva Endocrinol 2019; 44: 129-136